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Oral administration of nanoparticles (NPs) is a promising strategy to overcome solubility and stability issues of many active compounds. However, this route faces major obstacles related to the hostile gastrointestinal (GI) environment, which impairs the efficacy of orally administered nanomedicines. Here, we propose nanocomposites as a promising approach to increase the retention time of NPs in the intestinal tract by using bio- and mucoadhesive matrixes able to protect the cargo until it reaches the targeted area. A microfluidic-based approach has been applied for the production of tailored nanoemulsions (NEs) of about 110 nm, used for the encapsulation of small hydrophobic drugs such as the anti-inflammatory JAK-inhibitor tofacitinib. These NEs proved to be efficiently internalized into a mucus-secreting human intestinal monolayer of Caco-2/HT29-MTX cells and to deliver tofacitinib to subepithelial human THP-1 macrophage-like cells, reducing their inflammatory response. NEs were then successfully encapsulated into alginate hydrogel microbeads of around 300 μm, which were characterized by rheological experiments and dried to create a long-term stable system for pharmaceutical applications. Finally, ex vivo experiments on excised segments of rats' intestine proved the bioadhesive ability of NEs embedded in alginate hydrogels compared to free NEs, showing the advantage that this hybrid system can offer for the treatment of intestinal pathologies.

Ion sensitive field effect transistors (ISFETs) form a very attractive solution for wearable sensors due to their capacity for ultra-miniaturization, low power operation, and very high sensitivity, supported by complementary metal oxide semiconductor (CMOS) integration. This paper reports for the first time, a multianalyte sensing platform that incorporates high performance, high yield, high robustness, three-dimensional-extended-metal-gate ISFETs (3D-EMG-ISFETs) realized by the postprocessing of a conventional 0.18 μm CMOS technology node. The detection of four analytes (pH, Na + , K + , and Ca 2+ ) is reported with excellent sensitivities (58 mV/pH, -57 mV/dec(Na + ), -48 mV/dec(K + ), and -26 mV/dec(Ca 2+ )) close to the Nernstian limit, and high selectivity, achieved by the use of highly selective ion selective membranes based on postprocessing integration steps aimed at eliminating any significant sensor hysteresis and parasitics. We are reporting simultaneous time-dependent recording of multiple analytes, with high selectivities. In vitro real sweat tests are carried out to prove the validity of our sensors. The reported sensors have the lowest reported power consumption, being capable of operation down to 2 pW/sensor. Due to the ultralow power consumption of our ISFETs, we achieve and report a final four-analyte passive system demonstrator including the readout interface and the remote powering of the ISFET sensors, all powered by an radio frequency (RF) signal.

Wearable systems could offer noninvasive and real-time solutions for monitoring of biomarkers in human sweat as an alternative to blood testing. Recent studies have demonstrated that the concentration of certain biomarkers in sweat can be directly correlated to their concentrations in blood, making sweat a trusted biofluid candidate for noninvasive diagnostics. We introduce a fully on-chip integrated wearable sweat sensing system to track biochemical information at the surface of the skin in real time. This system heterogeneously integrates, on a single silicon chip, state-of-the-art ultrathin body (UTB) fully depleted silicon-on-insulator (FD-SOI) ISFET sensors with a biocompatible microfluidic interface, to deliver a "lab-on-skin" sensing platform. A full process for the fabrication of this system is proposed in this work and is demonstrated by standard semiconductor fabrication procedures. The system is capable of collecting small volumes of sweat from the skin of a human and posteriorly passively driving the biofluid, by capillary action, to a set of functionalized ISFETs for analysis of pH level and Na + and K + concentrations. Drop-casted ion-sensing membranes on different sets of sensors on the same substrate enable multiparameter analysis on the same chip, with small and controlled cross-sensitivities, whereas a miniaturized quasireference electrodes set a stable analyte potential, avoiding the use of a cumbersome external reference electrode. The progress of lab-on-skin technology reported here can lead to autonomous wearable systems enabling real-time continuous monitoring of sweat composition, with applications ranging from medicine to lifestyle behavioral engineering and sports.